This is a cooperative project to isolate, identify, and study pharmacological and chemical properties of cardiotonic agents found primarily among certain species of the phylum Coelenterata from the Pacific. Three different polypeptides (AP-A, AP-B and AP-C) have been isolated in pure state and characterized. All show positive inotropic effect, and AP-A has been studied pharmacologically in detail. The plan is to isolate additional active agents (nine of thirteen species have shown positive inotropic effect) looking primarily for substances with activity and safety as good as AP-A but with lower molecular weight so that oral activity may be achieved and synthesis is practical. AP-A will also be segmented both chemically and enzymatically in an attempt to achieve the same objective. For the proteins and polypeptides, gel permeation, ion-exchange and adsorption chromatography have been found to be useful separation procedures. Procedures are monitored by isolated atria bioassay and, once determined, electrophoretic properties. Pharmacological studies of the most promising purified drugs will be similar to those already carried out with AP-A and will include: Acute toxicity (LD50, 24 hrs.); inotropic effect in isolated atria; blood pressure; blood pressure; heart rate and cardiac contractility in situ; adrenergic mechanism (or lack thereof); heart-lung preparations; anti-arrhythmic action; electrophysiology of the heart (microelectrode technique); isolated vascular smooth muscle; Ca ions flux; Ca ions binding; enzyme inhibition (Na, K-ATPase, MAO, COMT, PDE); effect on cyclic AMP concentrations; effects on Mn ions, La ions and Verapamil; Ca 45 uptake. Long term objective: to obtain a superior cardiotonic agent for parenteral and oral use, and for pharmacological research.